A fundamental principle of cell biology is that complex behaviors such as cell growth, differentiation, motility, and apoptosis are controlled by receptor-mediated signal transduction, which impacts gene expression, protein synthesis, and cell metabolism by triggering a series of molecular-mediated intracellular signaling cascades. Receptor-mediated signal transduction allows cells to convert one type of stimulus into a different type of stimulus, the receptor acting as the intermediary in carrying out the conversion. Such transduction is often triggered by the binding of chemical ligands, such as hormones, cytokines, and adhesive macromolecules to cell surface receptors and propagated by specific binding of different molecules inside the cell. Hence, conventional approaches to transduction-mediated cellular control have relied upon the use of these chemical cues.
Although living cells exhibit a capacity for signal detection and information processing far beyond that of man-made technologies, one of the major limitations in developing living cells as signal detectors has been the lack of a suitable control interface between cells and existing microtechnologies. But these natural chemical signals are not always well-suited in microtechnologies, however, such as medical devices, drug delivery systems, biocomputers, man-machine interfaces, and other techniques that incorporate living cells as system components. To be effective, cellular devices require actuation mechanisms that are much more robust, non-invasive, and relatively free of side effects. For efficacy, cellular devices also require actuation mechanisms that are easy to interface with physical inputs, rather than chemical inputs. Chemical cues are also distributed throughout the entire body when injected into patients, and thus they do not provide spatial control of their actions when used clinically.
A few highly specialized cell types, including neurons and myocytes, have been activated using electrical stimuli, and microelectrode arrays have been developed in attempts to influence the activity of these cells in microdevices and in patients. Most cells are not electrically active in this way, however, and switches activated by electrical signals have high power requirements, so this approach may not be generalized for cellular microsystems design. Medical microdevices that require electrical stimulation also often require indwelling wires or transcutaneous electrodes that can lead to medical complications, such as infection.
None of the current approaches provides for highly practical or portable devices that overcome the above deficiencies nor mechanisms to provide spatial control over chemical signaling behaviors in cells in vivo, and past approaches have fallen short in that no suitable cellular actuation mechanism exists that is more robust, non-invasive, and easy to interface with physical inputs. Likewise, prior attempts have not been successful in producing low-power actuation mechanisms to initiate cellular signaling. Magnetic systems offer this form of non-invasive control with minimal power requirements, and thus, there is a need for systems and methods for magnetic control technologies to rapidly and reversibly control a wide range of cellular signal transduction pathways that would overcome these limitations, such as a magnetic actuation mechanism that is broadly applicable to a vast array of cell types and receptor systems useful, for example, for magnetodynamic therapy.